In a retrospective analysis of a major radiation therapy trial, more than four-fifths of patients whose tumors were HPV-positive were alive three years after treatment, according to Maura Gillison, MD, PhD, of Ohio State University in Columbus, and colleagues.

In contrast, fewer than six of 10 patients with HPV-negative tumors were still alive at the three-year mark, Gillison and colleagues reported online in the New England Journal of Medicine, in an article released to coincide with a presentation at the American Society of Clinical Oncology meeting here.

The study follows a report earlier at the meeting that found a similar pattern among patients enrolled in a chemotherapy trial. The virus is, of course, well known to cause cervical cancer.

The New England Journal study adds to the evidence that "HPV-positive oropharyngeal squamous-cell carcinoma represents a distinct clinicopathological entity associated with a better prognosis than HPV-negative oropharyngeal squamous-cell carcinoma," said Douglas Lowy, MD, of the NIH, and Karl Munger, PhD, of Brigham and Women's Hospital in Boston.

Writing in an accompanying editorial, Lowy and Munger argued that if the diseases are distinct, "their treatment or prevention might benefit from different approaches."

One possibility, they said, would be to target HPV proteins to treat the disease in some patients, while prevention might involve vaccination against the virus.

Gillison and colleagues looked at the Radiation Therapy Oncology Group 0129, a randomized study testing accelerated-fractionation radiotherapy against standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck.

Over a median of 4.8 years of follow-up, the study found no significant differences in survival between the two types of radiation therapy, Gillison and colleagues noted.

For this analysis, they looked at the 60.1% of patients -- 433 of 721 -- who had oropharyngeal cancer. Of those, HPV status was available for 323 patients, they said, including 206 whose tumors were HPV-positive.

Analysis showed that the HPV-positive patients had better three-year rates of overall survival than those with HPV-negative tumors -- 82.4% compared with 57.1%. The difference was significant at P<0.001 by the log-rank test.

After adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, those with HPV-positive tumors had a 58% reduction in the risk of death (HR 0.42, 95% CI 0.27 to 0.66).

Tobacco smoking was also a significant predictor of death (at P<0.001), with the risk increasing by 1% for each additional pack-year smoked, the researchers found, and the magnitude of the effect was the same regardless of HPV-status.

One implication of the study, the researchers said, is that future clinical trials of new treatments should be designed to stratify patients on the basis of HPV status.

The study was supported by the National Cancer Institute, the National Institute of Dental and Craniofacial Research, and the Oral Cancer Foundation.

Gillison is an employee of the National Institute of Dental and Craniofacial Research.